Bottom Line:
There is evidence that an inflammatory microenvironment is associated with the development and progression of prostate cancer (PCa), although the determinants of intrinsic inflammation in PCa cells are not completely understood.In DU145 and PC-3 cell lines expressing mPGES-1 (mPGES-1(SC) cells), we demonstrate that silencing or 'knock down' of mPGES-1 (mPGES-1(KD)) or pharmacological inhibition by MF63 strongly attenuates overall oncogenic drive.Indeed, mPGES-1(SC) cells express stem-cell-like features (high CD44, β1-integrin, Nanog and Oct4 and low CD24 and α6-integrin) as well as mesenchymal transition markers (high vimentin, high fibronectin, low E-cadherin).

Mentions:
We investigated the correlation of mPGES-1 expression (immunohistochemistry) with staging and grading in a series of PCa cases. Overall, mPGES-1 expression was detected in 12/25 (48%) organ-confined PCa and in 21/27 (77.7%) advanced PCa (Fig. 1A). In human advanced PCa samples, both mPGES-1 and EGFR were co-expressed in a high percentage of cases (n=19/27, 70.3%; Fig. 1A). In the same group, α6-integrin, a stem cell marker (Marthick & Dickinson 2012, Hoogland et al. 2014), was negative or weakly stained (n=19/27; Fig. 1B). By contrast, only 7/25 (28%) of organ-confined tumours showed co-expression of mPGES-1 and EGFR (Fig. 1A, 70.3% vs 28%, see also panel a and b from an organ confined PCa sample vs c and d from an advanced PCa sample).

Mentions:
We investigated the correlation of mPGES-1 expression (immunohistochemistry) with staging and grading in a series of PCa cases. Overall, mPGES-1 expression was detected in 12/25 (48%) organ-confined PCa and in 21/27 (77.7%) advanced PCa (Fig. 1A). In human advanced PCa samples, both mPGES-1 and EGFR were co-expressed in a high percentage of cases (n=19/27, 70.3%; Fig. 1A). In the same group, α6-integrin, a stem cell marker (Marthick & Dickinson 2012, Hoogland et al. 2014), was negative or weakly stained (n=19/27; Fig. 1B). By contrast, only 7/25 (28%) of organ-confined tumours showed co-expression of mPGES-1 and EGFR (Fig. 1A, 70.3% vs 28%, see also panel a and b from an organ confined PCa sample vs c and d from an advanced PCa sample).

Bottom Line:
There is evidence that an inflammatory microenvironment is associated with the development and progression of prostate cancer (PCa), although the determinants of intrinsic inflammation in PCa cells are not completely understood.In DU145 and PC-3 cell lines expressing mPGES-1 (mPGES-1(SC) cells), we demonstrate that silencing or 'knock down' of mPGES-1 (mPGES-1(KD)) or pharmacological inhibition by MF63 strongly attenuates overall oncogenic drive.Indeed, mPGES-1(SC) cells express stem-cell-like features (high CD44, β1-integrin, Nanog and Oct4 and low CD24 and α6-integrin) as well as mesenchymal transition markers (high vimentin, high fibronectin, low E-cadherin).